Over the past four decades, we have been studying the chemistry of defense and communication among terrestrial insects and other arthropods, a group of organisms that includes over half of all described species on earth. While many of the compounds we have characterized have simple structures (such as straight chain alkenes, carboxylic acids, aldehydes, phenols, benzoquinones), there are also many examples of biologically active alkaloids, isoprenoids (including steroids), and polypeptides with novel structures which we have discovered in the course of this research. We plan to select approximately ten of the most interesting structures and to prepare pilot-scale libraries consisting of the natural product itself plus -5-30 related structures in quantities suitable for high throughput screening. This project is the culmination, from the viewpoint of drug discovery, of our many years of research in the field of natural products chemistry. ds and proposed derivatives generally represent molecular structures that have not yet been examined via high throughput screening. The likelihood of discovering activities within these libraries of relevance to areas such as neuron-pharmacology, infectious and parasitic diseases, or cancer is much greater than would be expected from a study of other areas of chemical space which are not based on small molecules of biological origin. 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